Trametinib

Trametinib is a selective inhibitor of the MEK1 and MEK2 enzymes in the MAPK/ERK signaling pathway. It is an oral anticancer medication marketed under the brand name Mekinist and developed by Novartis. By blocking MEK1/2 activity, trametinib reduces ERK phosphorylation and downstream cell proliferation, particularly in tumors driven by activating BRAF mutations.

Indications and use: Trametinib is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, usually in combination with the BRAF inhibitor dabrafenib. The combination therapy has also been approved for other BRAF V600E/K-mutant cancers, including certain cases of non-small cell lung cancer, and is used in adults and, in some indications, select pediatric patients.

Dosing and administration: Trametinib is taken orally once daily. When used in combination therapy with dabrafenib, the typical regimen is trametinib 2 mg once daily plus dabrafenib 150 mg twice daily. For some settings, trametinib may be used as monotherapy at a 2 mg daily dose. Dosing may be adjusted based on adverse effects, hepatic impairment, and clinical response.

Adverse effects and safety: Common side effects include rash or dermatitis, diarrhea, fatigue, edema, alopecia, nausea, and vomiting. Serious adverse events can involve cardiomyopathy with reduced left ventricular ejection fraction, interstitial lung disease, ocular toxicity (such as retinal events), hemorrhage, and hematologic abnormalities. Regular monitoring of cardiovascular, pulmonary, hepatic, and ocular status is recommended, and caution is advised when used with other targeted therapies due to potential interactions and pharmacodynamic effects.

Pharmacology and status: Trametinib is administered orally and achieves systemic exposure with a long elimination profile. It is approved in the United States, European Union, and other regions for specified BRAF-mutant cancers, alone or in combination with dabrafenib.